Uncovering the role of Cleft lip and palate transmembrane protein 1 (CLPTM1) in macrophage’s inflammatory response to infection

The Cleft lip and palate transmembrane protein 1 (Clptm1) is a multi-transmembrane protein associated with the common genetic birth defect Cleft lip with or without a cleft palate. Although its function remains almost entirely unknown, Clptm1 was previously described as a lipid scramblase required for efficient glycosylphosphatidylinositol biosynthesis or cancer mutations. Unexpectedly, it is highly expressed in immune cells, including lymphocytes, dendritic cells, and macrophages, when it is described as a TLR4-responsive gene. Interestingly, CLPTM1 was found to bind and trap GABAA receptors in the endoplasmic reticulum (ER), reducing its plasma membrane expression[1]. Recently, GABA transporter (GAT2) was shown to modulate macrophage pro-inflammatory function while its deficiency lowers interleukin-1b production ex-vivo and attenuated macrophage-mediated inflammatory responses to lipopolysaccharide (LPS) in-vivo[2]. This project aims to examine whether CLPTM1 takes part in the regulation of macrophage pro-inflammatory response to LPS. Using specific antibodies and Fluorescence-activated cell sorting (FACS), our preliminary data show that CLPTM1 is strongly expressed in human immune cells (exceptionally in monocytes) and mouse macrophages. Immunofluorescence (IF) and western blot assays confirmed its predicted membrane localization and indicated that upon LPS stimulation, its expression is repressed, supporting the possibility that Clptm1 is a negative regulator moderating the immune response prior TLR-4 activation.